Targeted inhibitor shows potential for RET-altered solid tumors
medwireNews: A selective inhibitor of the receptor tyrosine kinase RET could benefit patients with tumors harboring alterations in the oncogene, suggest early results presented at the American Association for Cancer Research Annual Meeting 2018.
Speaking to the press in Chicago, Illinois, USA, presenter Vivek Subbiah (The University of Texas MD Anderson Cancer Center in Houston, USA) explained that “RET-altered cancers across multiple tumor types represent a high medical need, as there are no approved agents that selectively target this oncogene.”
He added: “Current therapies for RET-altered cancers are restricted to multikinase inhibitors and chemotherapy, which are nonspecific and display significant off-target toxicity.
“In an effort to revolutionize treatment for these cancers, BLU-667 was designed to specifically target oncogenic RET fusions and activating mutations.”
In the phase I ARROW study, 29 patients with medullary thyroid cancer, 19 with non-small-cell lung cancer, two with papillary thyroid cancer, and one with paraganglioma – all carrying alterations in RET – were given BLU-667 orally at doses of 30–400 mg/day.
Of the 40 participants that could be evaluated for response at data cutoff, one achieved a complete response, while 17 patients had a partial response and 20 had stable disease. Only two patients progressed in response to treatment with BLU-667.
Subbiah noted that the selective inhibitor has “broad anti-tumor activity,” with responses seen across different tumor types and RET genotypes, regardless of the type of prior therapy.
BLU-667 also has “favorable tolerability,” he added. Most adverse events tended to be of grade 1, with constipation and elevations in alanine aminotransferase the most frequent, occurring in 20% of patients each. Treatment-related adverse events of grade 3 were reported in 16% of study participants, and no patients experienced events of grade 4 or 5.
In conclusion, Subbiah said that these “dose escalation data validate BLU-667 as a promising precision therapy for RET-altered cancers,” noting that the dose expansion stage of ARROW “is open and enrolling globally.”
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